Optimization and antifungal activity of quinoline derivatives linked to chalcone moiety combined with FLC against Candida albicans.

In present work, a series of quinoline derivatives linked to chalcone moiety have been prepared, and their in vitro and in vivo antifungal activities against C. albicans have been evaluated. The results indicated that quinoline combined with fluconazole (FLC) showed good inhibitory activity against C. albicans. Especially, compound PK-10 combined with FLC displayed the best antifungal activity against 14 FLC-resistant C. albicans strains with almost no cytotoxicity. Preliminary mechanistic studies proved that PK-10 combined with FLC could inhibit the hyphae formation of C. albicans, induce the accumulation of reactive oxygen species (ROS), the damage of mitochondrial membrane potential and the decrease of intracellular ATP content, which led to mitochondrial dysfunction. In vivo studies found obvious effects of the co-treatment regimen had obvious effects based on histological analysis, body weight curves, and coefficients of major organs. Therefore, the optimization of quinolone-chalcone derivatives combined with FLC could exert the potent antifungal activity in vitro and in vivo obviously, suggesting them as new agents to treat drug-resistant C. albicans infection.

Antifungal evaluation of quinoline-chalcone derivatives combined with FLC against drug-resistant Candida albicans.

With the widespread clinical use of FLC, the FLC-resistant C. albicans greatly increases the difficulty of treatment, and drug combination becomes an important method to treat C. albicans infection. In this work, we have prepared a series of quinoline-chalcone derivatives in good yields, and in vitro antifungal activity against C. albicans were evaluated. The results indicated that most title compounds combined with FLC showed good antifungal activity against drug-resistant C. albicans. Further mechanism researches demonstrated that 6a and 6c combined with FLC could significantly inhibited growth and biofilm formation of C. albicans, induce ROS accumulation, impair the mitochondrial membrane, and decrease intracellular ATP concentrations.

Dynamic Mitochondrial Proteome Under Polyamines Treatment in Cardiac Aging.

Age-related alteration of mitochondria causes impaired cardiac function, along with cellular and molecular changes. Polyamines can extend the life span in mice. However, whether polyamines can affect the dynamic mitochondrial proteome, thereby preventing age-related changes in cardiac function and cardiac aging, remains unclear. In this study, we found that spermine (Spm) and spermidine (Spd) injection for 6 weeks could prevent 24-month-old rats heart dysfunction, improve mitochondrial function, and downregulate apoptosis. Using iTRAQ tools, we identify 75 mitochondrial proteins of statistically significant alteration in aging hearts, which mainly participate in important mitochondrial physiological activity, such as metabolism, translation, transport, apoptosis, and oxidative phosphorylation. Moreover, four proteins of differential expression, pyruvate dehydrogenase kinase (PDK4), trifunctional enzyme subunit alpha (HADHA), nicotinamide nucleotide transhydrogenase (NNT), and Annexin6, which were significantly associated with heart aging, were validated by Western blotting. In vitro, we further demonstrated polyamines could retard cardiomyocytes aging through downregulating the expression of PDK4 and thereby inhibiting cell apoptosis. In summary, the distinct mitochondrial proteins identified in this study suggested some candidates involved in the anti-aging of the heart after polyamines treatment, and PDK4 may provide molecular clues for polyamines to inhibit apoptosis and thus retard aging-induced cardiac dysfunction.

Spermidine Alleviates Intrauterine Hypoxia-Induced Offspring Newborn Myocardial Mitochondrial Damage in Rats by Inhibiting Oxidative Stress and Regulating Mitochondrial Quality Control.

Background: Intrauterine hypoxia (IUH) increases the risk of cardiovascular diseases in offspring. As a reactive oxygen species (ROS) scavenger, polyamine spermidine (SPD) is essential for embryonic and fetal survival and growth. However, further studies on the SPD protection and mechanisms for IUH-induced heart damage in offspring are required. Objectives: This study aimed to investigate the preventive effects of prenatal SPD treatment on IUH-induced heart damage in newborn offspring rats and its underlying mitochondrial-related mechanism. Methods: The rat model of IUH was established by exposure to 10% O2 seven days before term. Meanwhile, for seven days, the pregnant rats were given SPD (5 mg.kg-1.d-1; ip). The one-day offspring rats were sacrificed to assess several parameters, including growth development, heart damage, cardiomyocytes proliferation, myocardial oxidative stress, cell apoptosis, and mitochondrial function, and have mitochondrial quality control (MQC), including mitophagy, mitochondrial biogenesis, and mitochondrial fusion/fission. In in vitro experiments, primary cardiomyocytes were subjected to hypoxia with or without SPD for 24 hours. Results: IUH decreased body weight, heart weight, cardiac Ki67 expression, the activity of SOD, and the CAT and adenosine 5'-triphosphate (ATP) levels and increased the BAX/BCL2 expression, and TUNEL-positive nuclei numbers. Furthermore, IUH also caused mitochondrial structure abnormality, dysfunction, and decreased mitophagy (decreased number of mitophagosomes), declined mitochondrial biogenesis (decreased expression of SIRT-1, PGC-1α, NRF-2, and TFAM), and led to fission/fusion imbalance (increased percentage of mitochondrial fragments, increased DRP1 expression, and decreased MFN2 expression) in the myocardium. Surprisingly, SPD treatment normalized the variations in the IUH-induced parameters. Furthermore, SPD also prevented hypoxia-induced ROS accumulation, mitochondrial membrane potential decay, and the mitophagy decrease in cardiomyocytes. Conclusion: Maternal SPD treatment caused IUH-induced heart damage in newborn offspring rats by improving the myocardial mitochondrial function via anti-oxidation and anti-apoptosis, and regulating MQC.

Effects and mediating mechanisms of a structured limbs-exercise program on general cognitive function in older adults with mild cognitive impairment: A randomized controlled trial.

BACKGROUND: Exercise is known to prevent cognitive decline. Sleep quality and depression symptoms, which are associated with processing speed, are considered as common mediators in the exercise-cognition putative model. However, these mediating mechanisms have not been empirically tested in an intervention study. OBJECTIVE: The aim of this study was to evaluate the effects of a structured limbs-exercise program on general cognitive function, and to test the mediating effects and mediating pathways of depressive symptoms, sleep quality and processing speed in the relationship of exercise-induced cognitive benefits. DESIGN: A two-arm and assessor-blinded randomized controlled trial. SETTINGS AND PARTICIPANTS: Community-dwelling older adults with mild cognitive impairment living in an urban area in Chifeng, China. METHODS: Participants (N=116) were randomly allocated to one of the two arms: (1) a 24-week structured limbs-exercise program (3 supervised limb exercise sessions /week, 60 min /session for the first 12 weeks and 3 unsupervised practice sessions /week, 60 min /session for the following 12 weeks) or (2) health promotion classes alone. Measures of depressive symptoms, sleep quality, processing speed, and general cognitive function were collected at baseline, 12-week, and 24-week. Multivariate analysis of variance and structural equation modeling was used to test the effectiveness and mechanisms of structured limbs-exercise-induced cognitive improvement respectively. RESULTS: The structured limbs-exercise program was beneficial for maintaining general cognitive function at 12 weeks (mean difference = 1.20, 95% CI [0.354, 2.054], p = 0.006) and at 24 weeks (mean difference = 1.59, 95% CI [0.722, 2.458], p = 0.001) in the intervention group. The results from the goodness-of-fit indices of structural equation modeling show as following: (1) The effect of structured limbs-exercise program on cognitive function was partially mediated by depressive symptoms, sleep quality, and processing speed, with 69.22% of joint mediation proportion; (2) Relative to the combined Z values of depressive symptoms and processing speed, sleep quality was more strongly related to cognitive function in the structured limbs-exercise program (Z= 9.294, p<0.01); (3) Processing speed was affected by depressive symptoms, sleep quality, and in turn, yielding a significant effect on cognitive function; and (4) Five potential mediating pathways for improvement in general cognitive function in the structured limbs-exercise intervention were identified. CONCLUSION: This study shows that this exercise program can maintain general cognitive function for older adults with mild cognitive impairment. Mediating variables include depressive symptoms, sleep quality and processing speed. Future research should continue to incorporate path-oriented intervention strategies in the exercise intervention to maximize improvements in cognitive function. Registration number: ChiCTR1800016299.

Sleep disturbance and quality of life in clinically stable inpatients with schizophrenia in rural China.

BACKGROUND: Studies have identified numerous factors that may affect the sleep quality and quality of life (QOL) in outpatients with schizophrenia. However, the clinically stable inpatients who represent a large proportion of the population with schizophrenia in China have not received enough attention. The present study was performed to explore the sociodemographic and clinical correlates of sleep disturbance and QOL in clinically stable inpatients with schizophrenia in rural China. METHODS: A cross-sectional study was designed, and 207 clinically stable inpatients with schizophrenia were selected from Chifeng Anding Hospital, located in Inner Mongolia Autonomous Region, in northern China. All subjects were interviewed by the same investigator using standardized assessment instruments. QOL and sleep disturbance were measured using the Schizophrenia Quality of Life Scale (SQLS) and Pittsburgh Sleep Quality Index (PSQI), respectively. Univariate and multiple regression analyses were used to identify the factors influencing sleep disturbance and QOL. Antipsychotics taken by individuals were converted into olanzapine equivalent doses as the main confounding factor to be controlled. RESULTS: The prevalence of sleep disturbance was 58%, and sleep disturbance was significantly associated with depression (OR 1.33, 95% CI 1.17-1.52) and coping mechanisms (OR 0.95, 95% CI 0.91-0.98). We observed large differences between the sexes: the QOL of male inpatients with schizophrenia was substantially better than that of female inpatients, with a standard coefficient of 0.19 ± 1.62. Other factors related to QOL were depression (0.42 ± 0.30), hope (- 0.21 ± 0.19), general psychopathology symptoms (0.21 ± 0.24) and personal and social performance (- 0.12 ± 0.07). CONCLUSIONS: The depressive symptoms of inpatients with schizophrenia should receive more attention. More targeted interventions, such as the early identification and treatment of depression, should be promptly administered to improve the patient's hospitalization experience.

Mediation and moderation analyses: exploring the complex pathways between hope and quality of life among patients with schizophrenia.

BACKGROUND: The underlying mechanism between hope and quality of life is as yet unknown. We aim to examine the potential mediating effect of depression and resilience and the moderated effect of sex in this well-established association. METHODS: Two hundred seven patients diagnosed with schizophrenia were administered a questionnaire battery that measured hope, depression, resilience and QOL. A multiple mediation model was used to examine the mediating effect of resilience and depression on the association between hope and QOL. A subgroup analysis was performed and a moderated mediation model was examined to find and test the moderated effect of sex on the mediation model. We used Mplus to perform moderation and mediation analyses so that the mediators and moderator could function together in the same model. RESULT: Sex was the moderator on the direct path between hope and QOL. The relationship between hope and QOL was mediated by resilience and depression in both sexes. When compared with female patients, the effect of hope on QOL was completely mediated by resilience and depression in males. In female patients, the model was partially mediated, and the direct effect of hope on QOL was significantly negatively correlated with the level of hope. CONCLUSION: We present a conceptual model containing the mediated effects of resilience and depression and the moderated effect of sex between hope and QOL, which we believe facilitates the understanding of these associations. This model should be useful in the formulation of strategies to improve QOL.

Corrigendum to "Spermidine Prevents Heart Injury in Neonatal Rats Exposed to Intrauterine Hypoxia by Inhibiting Oxidative Stress and Mitochondrial Fragmentation".

[This corrects the article DOI: 10.1155/2019/5406468.].

Cognitive-behavioural therapy for personal recovery of patients with schizophrenia: A systematic review and meta-analysis.

BACKGROUND: To date, cognitive-behavioural therapy (CBT) trials have primarily focused on clinical recovery; however, personal recovery is actually the fundamental aspect of the recovery process. The aim of this study was to summarise and synthesise the existing evidence regarding the effectiveness of CBT for personal recovery in patients with schizophrenia. AIM: This study aimed to determine the effectiveness of CBT for personal recovery in patients with schizophrenia. METHODS: A systematic search of the literature in PsycINFO, PubMed, Cochrane (CENTRAL), Embase and Web of Science (SCI) was conducted to identify randomised controlled trials reporting the impact of CBT interventions on personal recovery in patients with schizophrenia. The estimated effect sizes of the main study outcomes were calculated to estimate the magnitude of the treatment effects of CBT on personal recovery. We also evaluated the CBT's effect size at the end-of-treatment and long-term (follow-up) changes in some aspects of personal recovery. RESULTS: Twenty-five studies were included in the analysis. The effect of CBT on personal recovery was 2.27 (95% CI 0.10 to 4.45; I2=0%; p=0.04) at post-treatment and the long-term effect size was 2.62 (95% CI 0.51 to 4.47; I2=0%; p=0.02). During the post-treatment period, the pooled effect size of CBT was 0.01 (95% CI -0.12 to 0.15; I2=33.0%; p>0.05) for quality of life (QoL), 0.643 (95% CI 0.056 to 1.130; I2=30.8%; p<0.01) for psychological health-related QoL, -1.77 (95% CI -3.29 to -0.25; I2=40%; p=0.02) for hopelessness and 1.85 (95% CI 0.69 to 3.01; I2=41%; p<0.01) for self-esteem. We also summarised the effects of CBT on QoL (subscale scores not included in the evaluation of the pooled effect size), self-confidence and connectedness, and all results corresponded to positive effects. However, there was insufficient evidence regarding the long-term effects of CBT on personal recovery. CONCLUSIONS: CBT is an effective therapy with meaningful clinical effect sizes on personal recovery and some aspects of personal recovery of schizophrenia after treatment. However, the effect is relatively immediate and rapidly decreases as time progresses. Therefore, in the future, more studies should focus on the mechanism of CBT for personal recovery and the factors that influence the long-term effects of CBT. TRIAL REGISTRATION NUMBER: CRD42018085643.

Spermidine Prevents Heart Injury in Neonatal Rats Exposed to Intrauterine Hypoxia by Inhibiting Oxidative Stress and Mitochondrial Fragmentation.

Intrauterine hypoxia (IUH) is a common intrauterine dysplasia that can cause programming of the offspring cardiovascular system. In this study, we hypothesized that placental treatment with spermidine (SPD) can prevent heart injury in neonatal offspring exposed to IUH. Pregnant rats were exposed to 21% O2 or 10% O2 (hypoxia) for 7 days prior to term or were exposed to hypoxia and intraperitoneally administered SPD or SPD+difluromethylornithine (DFMO) on gestational days 15-21. Seven-day-old offspring were then sacrificed to assess several parameters. Our results demonstrated that IUH led to decreased myocardial ornithine decarboxylase (ODC) and increased spermidine/spermine N1-acetyltransferase (SSAT) expression in the offspring. IUH also resulted in decreased offspring body weight, heart weight, cardiomyocyte proliferation, and antioxidant capacity and increased cardiomyocyte apoptosis and fibrosis. Furthermore, IUH caused mitochondrial structure abnormality, dysfunction, and decreased biogenesis and led to a fission/fusion imbalance in offspring hearts. In vitro, hypoxia induced mitochondrial ROS accumulation, decreased membrane potential, and increased fragmentation. Notably, all hypoxia-induced changes analyzed in this study were prevented by SPD. Thus, in utero SPD treatment is a potential strategy for preventing IUH-induced neonatal cardiac injury.

Spermine and spermidine reversed age-related cardiac deterioration in rats.

Aging is the most important risk factor for cardiovascular disease (CVD). Slowing or reversing the physiological impact of heart aging may reduce morbidity and mortality associated with age-related CVD. The polyamines, spermine (SP) and spermidine (SPD) are essential for cell growth, differentiation and apoptosis, and levels of both decline with age. To explore the effects of these polyamines on heart aging, we administered SP or SPD intraperitoneally to 22- to 24-month-old rats for 6 weeks. Both treatments reversed and inhibited age-related myocardial morphology alterations, myocardial fibrosis, and cell apoptosis. Using combined proteomics and metabolomics analyses, we identified proteins and metabolites up- or downregulated by SP and SPD in aging rat hearts. SP upregulated 51 proteins and 28 metabolites while downregulating 80 proteins and 29 metabolites. SPD upregulated 44 proteins and 24 metabolites and downregulated 84 proteins and 176 metabolites. These molecules were mainly associated with immune responses, blood coagulation, lipid metabolism, and glutathione metabolism pathways. Our study provides novel molecular information on the cardioprotective effects of polyamines in the aging heart, and supports the notion that SP and SPD are potential clinical therapeutics targeting heart disease.